This project involves the identification of specific anthracycline antibiotic macromolecular interactions in cells and the characterization of the relationship of these associations to overall drug cytotoxic and cytostatic mechanisms. The unique biological interactions will be identified by in vitro and in situ covalent labeling with radioactive photoactive anthracycline antibiotic analogues by exposure to ultraviolet light. Specific radiolabeled macromolecules will be identified and their subcellular distribution determined. Anthracycline binding proteins (ABPs) will be purified, characterized and their normal physiological functions identified. The relationship of these specific cellular associations to drug analogue uptake, efflux, subcellular, localization and cytostatic activity in normal, malignant and drug resistant cells will be examined. A possible connection between ABPs and anthracycline antibiotic anti-cancer and drug resistant mechanisms will be sought.